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Aymé-Gripp syndrome (AYGRPS) is a multisystemic disorder caused by a subset of pathogenic variants in the MAF gene. Major clinical features include bilateral early cataracts, sensorineural hearing loss (SNHL), and a characteristic facial appearance along with variable neurodevelopmental delay. Pericarditis resulting in pericardial effusion of varying degree has been observed in a subset of affected individuals and could represent a severe feature in neonatal or infantile age. Here, we describe a syndromic infant with massive pericardial effusion and craniofacial features that oriented toward the suspicion of AYGRPS, which was subsequently confirmed by the molecular analysis of MAF. Pericardial effusion was first observed prenatally and documented to be recurrent, progressive, and severe in the first months of life, thus requiring pericardiocentesis and surgical procedures. In this report, we provide further delineation of the minor clinical characteristics, particularly focusing on cardiac features of AYGRPS. A dedicated cardiac surveillance of these findings may help reduce the morbidity and mortality of this rare condition., (© 2024 Wiley Periodicals LLC.)

Kinesin super family (KIF) genes encode motor kinesins, a family of evolutionary conserved proteins, involved in intracellular trafficking of various cargoes. These proteins are critical for various physiological processes including neuron function and survival, ciliary function and ciliogenesis, and cell-cycle progression. Recent evidence suggests that alterations in motor kinesin genes can lead to a variety of human diseases, including monogenic disorders. Neuropathies, impaired higher brain functions, structural brain abnormalities and multiple congenital anomalies (i.e., renal, urogenital, and limb anomalies) can result from pathogenic variants in many KIF genes. We expand the phenotype associated with KIF4A variants from developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of phenotypic manifestations. Additional anomalies of the kidneys and urinary tract, congenital lymphedema, eye, and dental anomalies seem to be variably associated and overlap with clinical signs observed in other kinesinopathies. Caution still applies to missense variants, but hopefully, future work will further establish genotype-phenotype correlations in a larger number of patients and functional studies may give further insights into the complex function of KIF4A., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Exome sequencing has led to the comprehension of the molecular bases of several forms of neurodevelopmental disorders, a clinically heterogeneous group of diseases characterized by intellectual disability (ID) and autism spectrum disorder (ASD). De novo mutations in POGZ has been causally linked to isolated ASD and syndromic ID, only recently. Here we report on a 15 year-old girl in whom exome sequencing allowed to identify a de novo POGZ truncating mutation as the molecular cause underlying a complex phenotype apparently not fitting any recognized syndrome. We describe the evolution of her clinical features with age, and review published clinical data of patients with POGZ mutations to systematically analyze the clinical spectrum associated with mutations. Our finding expands the clinical and molecular spectrum of POGZ mutations. Revision of the literature indicate that moderate to severe ID, microcephaly, variable CNS malformations, reduced growth, brachytelephalangy, and facial dysmorphism represent recurrent features associated with POGZ mutations., (© 2017 Wiley Periodicals, Inc.)